Lung cancer is most common in people who have been smokers. In up to 25% of cases, however, the patient has not smoked in their entire life.
Three distinct types of lung cancer have been identified in a large study that looked at these "never smokers". They appear to be caused by no environmental triggers like smoke, asbestos or pollution.
"What we are seeing is that there are distinct subtypes of lung carcinoma in never-smokers that have distinct molecular properties and evolutionary processes," Maria Teresa Landi, an epidemiologist at the United States' National Institute of Health.
"In the future, we might be able to offer different treatments based upon these subtypes."
Smoking has led to a global epidemic of lung cancer. 2 million cases are reported each year. However, it is still not clear how this disease occurs in people who have never smoked.
These non-smoker tumors have been identified by new research.
Scientists sequenced frozen tumor tissue from 232 people who had never smoked and were diagnosed with non-small-cell lung cancer. They discovered several mutational signatures not found in normal lung tissue.
These genetic changes are not the same as those that occur when tobacco smoke causes lung cancer. This suggests that an alternative cause of lung disease could be at play, possibly something happening in the body like faulty DNA repair, or oxidative stress.
Even the 62 never-smokers who were exposed to secondhand smoking showed similar signatures in their tumor tissue to those of other never-smokers. Although the sample is small, this indicates that their disease is caused by internal bodily changes, and not environmental stressors.
Landi admits that "we need a larger sample size and more detailed information about exposure to really study how secondhand tobacco smoking affects the development of lung carcinoma in never smokers."
This study also revealed that the majority of patients were of European descent. Future research will be required to increase diversity among its participants.
Nevertheless, the authors identified three new subtypes in their cohort of lung cancer.
Piano is the most common subtype, and it has the lowest number of genomic mutations. This subtype of lung carcinoma is linked to progenitor cells. These cells help to create new cells in your lungs. It can also grow slowly so it is easy to detect up to ten year in advance.
This second subtype is difficult to detect and grows very quickly. Because of its stronger and more complex genomic mutations, it has been called mezzo-forte. This form of lung cancer is thought to be caused by mutations in the growth factor receptor gene EGFR.
Fortuitous, which is the last subtype of nonsmoker lung carcinoma, is the most severe. It is also known to have a mutation called whole-genome double, which is common in lung cancers of smokers.
Even though the patient had smoked secondhand, their genomic signatures don't strongly match those who smoked.
Landi says, "We are just beginning to understand how these tumors develop." "This analysis shows heterogeneity or diversity in lung cancers among never-smokers."
If we are to properly treat lung cancer, it is important to understand how and why they occur naturally. Scientists are currently testing treatments to target mutations in EGFR genes. These could one day prove effective for mezzo-forte patients with naturally occurring lung cancer.
However, the piano subtype will be more difficult to treat because its genetic mutations appear to have multiple drivers. This makes it harder to target with drugs.
The authors still note that it is possible to find a pharmaceutical that blocks signals from the progenitor cells of the lungs, which could stop the growth and spread of piano tumors.
They hope that their research will inspire future drug research on lung cancers, particularly for people who have never smoked a cigarette.
Nature Genetics published the study.
